Respiration involves the introduction of fresh gases, especially oxygen, to the lung during inspiration and the removal of waste gases, particularly carbon dioxide, during expiration. In healthy individuals respiration is normally effected by spontaneous ventilation or breathing which results in the introduction of necessary gases. Unfortunately, a number of physiological and pathological processes may compromise normal pulmonary function leading to the inhibition of effective respiration or total respiratory failure. In such cases respiratory therapy, often involving artificial ventilation to some degree, is indicated. For example, respiratory therapy is often indicated for patients undergoing surgery or those suffering disorders and diseases of the pulmonary air passages. In particular, patients suffering from lung contusion, diver's lung, post-traumatic respiratory distress, post-surgical atelectasis, irritant injuries, septic shock, multiple organ failure, Mendelssohn's disease, obstructive lung disease, pneumonia, pulmonary edema or any other condition resulting in lung surfactant deficiency or respiratory distress are strong candidates for respiratory therapy. Typically, such respiratory therapy involves the use of mechanical ventilators.
Mechanical ventilators are clinical devices that effect ventilation or, in other words, cause air (or gas) flow in the lungs. More specifically, such devices typically force air into the lungs during the inspiration phase of the breathing cycle but allow a return to ambient pressure during spontaneous exhalation. The forced influx of fresh air by mechanical ventilation facilitates the pulmonary mediated processes that comprise respiration in mammals. One of these processes, removal of waste gases, is a primary mechanism by which carbon dioxide is excreted from the body. In normal gas mediated carbon dioxide removal, fresh air is brought into contact with the alveoli (alveolar ventilation) thereby promoting gas exchange wherein carbon dioxide passes from the body and is exhaled during the expiration phase of the breathing cycle. The other essential bioprocess, oxygenation, comprises the absorption of oxygen into the blood from the lungs. It is primarily a function of a mechanism whereby the partial pressure of oxygen (PO.sub.2) in pulmonary capillary blood equilibrates with the partial pressure of oxygen in inflated alveoli. The oxygen gradient between alveolus and capillary favors transfer of oxygen into blood because the repeated influx of fresh oxygen through ventilation (spontaneous or assisted) maintains alveolar PO.sub.2 at higher levels than capillary PO.sub.2. Modern mechanical ventilators are designed to provide ventilation by regulating tidal volume (breath), flow rate, delivery profile and respiratory flow thereby controlling carbon dioxide excretion. Because they can also regulate airway pressure and the concentration of inspired oxygen they offer control over oxygenation as well.
At least twenty makes and models of mechanical ventilators are used in North America today. Almost all the ventilators used in operating rooms, recovery rooms and intensive care units are volume-controlled ventilators. With a device of this type the operator may set tidal volume, respiratory rate, and inspiratory rate, allowing the ventilator to deliver a set volume of gas regardless of the airway pressure. Such devices usually have a pressure cutoff to prevent damage to the lungs. In contrast, pressure-controlled ventilators are standard in neonatal intensive care, in chronic ventilator management, and during patient transport. Pressure-controlled ventilators typically allow the operator to select the respiratory rate, the inspiratory gas flow and the peak airway pressure. The ventilator then delivers inspired gas, while monitoring the tidal volume, until the desired pressure is reached. Unfortunately, in both types of commercially available ventilators the expired gases, including any bioactive agents introduced during inspiration or exhaled pathogenic material, are typically released into the environment during use.
Another complication associated with conventional mechanical ventilation arises due to the composition of the delivered gases. Normally, inspired gas is conditioned by the upper respiratory tract and the trachea to ensure that it is saturated with water vapor prior to entering the delicate environment of the lower respiratory tract. In particular, the inspired gas is heated by convection in the upper respiratory tract while, at the same time, water vapor is added by evaporation. That is, the upper part of the airway acts as a thermoregulator adding heat and moisture to the inspired gas and extracting it from the exhaled gas. Unfortunately, mechanical ventilation often interferes with this natural physiological process by introducing cool unhumidified gas. This leads to dehydration of the respiratory tract potentially causing (1) impairment of ciliary activity; (2) impairment of mucus movement; (3) inflammatory changes and necrosis of the pulmonary epithelium; (4) bacterial infiltration; (5) atelectasis; and (6) pneumonia.
Due to the possible consequences, steps are typically taken to prevent the dehydration of the pulmonary surfaces during mechanical ventilation. Perhaps the most common step is actively pretreating the gas through the addition of water vapor and heat prior to pulmonary introduction. Another method of conditioning the gas as it is introduced into the lungs is through the use of passive heat and moisture exchangers. Heat and moisture exchange devices, or artificial noses, are used in medical applications to take up heat and moisture from a patient's exhaled breath and transfer it to inhaled gas. Specifically, they are designed to retain a portion of the expired moisture and heat and return it to the patient's respiratory tract during inspiration. Although they are produced using a number of different configurations, the present generation of exchange devices typically employs a hygroscopic element to absorb heat and moisture during expiration and release it as dry cool air from the ventilator passes over the element during inspiration.
The oldest and least efficient these devices is the heat and moisture exchanger (or HME) which consists of an aluminum insert and, optionally, a fibrous element. Because aluminum rapidly changes temperatures, moisture is deposited between the layers of the insert during exhalation. The retained heat and moisture is then returned, at least in part, during inhalation. Another type of exchange device is the heat and moisture exchanging filter (HMEF) which contains a hydrophobic fibrous insert that traps heat and adsorbs moisture on the patient side of the filter. Perhaps the most common type of exchange devices today are the hygroscopic condenser humidifiers (HGH) and hygroscopic condenser humidifying filters (HGHF) that use absorption to exchange heat and moisture. These devices comprise and element, typically paper, that is treated with lithium chloride or calcium chloride to increase the thermodynamic efficiency of the exchange. In the HGHF a bacterial filter is juxtaposed between the insert and the source of gas. While the use of artificial noses slightly increases flow resistance in the respiratory circuit, such devices have been found to provide safe and effective humidification for most patients.
Recently alternative techniques, particularly liquid ventilation, have been developed to obviate at least some of the complications associated with mechanical gas ventilation. In contrast to standard mechanical ventilation, liquid ventilation involves introducing an oxygenated liquid medium into the pulmonary air passages for the purposes of waste gas exchange and oxygenation. Essentially, there are two separate techniques for performing liquid ventilation, total liquid ventilation and partial liquid ventilation. Total liquid ventilation or "TLV" is the pulmonary introduction of warmed, extracorporeally oxygenated liquid respiratory promoter (typically fluorochemicals) at a volume greater than the functional residual capacity of the subject. The subject is then connected to a liquid breathing system and tidal liquid volumes are delivered at a frequency depending on respiratory requirements while exhaled liquid is purged of CO.sub.2 and oxygenated extracorporeally between the breaths. This often involves the use of specialized fluid handling equipment. Conversely, partial liquid ventilation or "PLV" involves the use of conventional mechanical ventilation in combination with pulmonary administration of a respiratory promoter capable of oxygenation. As with TLV, the respiratory promoter typically comprises fluorochemicals which may be oxygenated prior to introduction. In the instant application the term "liquid ventilation" will be used in a generic sense and shall be defined as the introduction of any amount of respiratory promoter into the lung, including the techniques of both partial liquid ventilation and total liquid ventilation.
Avoiding some of the complications associated with TLV, partial liquid ventilation, as described in Fuhrman, U.S. Pat. No. 5,437,272 and Faithfull et al. U.S. Pat. No. 5,490,498, is a safe and convenient clinical application of liquid breathing using fluorochemicals which are oxygenated in vivo. In PLV a liquid, vaporous or gaseous respiratory promoter (i.e. a fluorochemical) is introduced into the pulmonary air passages at volumes ranging from just enough to interact with a portion of the pulmonary surface all the way up to the functional residual capacity of the subject. Respiratory promoters are any compound that functions, systemically or pulmonarily, to improve gas exchange and respiration efficiency. Respiratory gas exchange is thereafter maintained for the duration of the procedure by continuous positive pressure ventilation using a conventional open-circuit gas ventilator. Like total liquid ventilation, the pulmonary introduction of the respiratory promoter eliminates surface tension due to pulmonary air/fluid interfaces while improving pulmonary function and gas exchange in surfactant deficiency and other disorders of the lung. As PLV does not require continued extracorporeal oxygenation, well established conventional off-the-shelf ventilators may be used to provide the necessary oxygenation and carbon dioxide purging in vivo. Moreover, as it is predominantly gas rather than liquid that moves in tidal fashion with each breath, the airway pressures required for the procedure may be much lower than during TLV. Finally, when the procedure is over the introduced the liquid, gaseous or vaporous respiratory promoter may be allowed to evaporate from the lung rather than being physically removed as in TLV.
As previously indicated, fluorochemicals are the preferred respiratory promoter for both TLV and PLV. Generally, fluorochemicals compatible with liquid ventilation will be clear, odorless, nonflammable, and essentially insoluble in water. Preferred fluorochemicals are denser than water and soft tissue, have a low surface tension and, for the most part, a low viscosity. In particular, many brominated fluorochemicals are known to be safe, biocompatible substances when appropriately used in medical applications. It is additionally known that oxygen, and gases in general, are highly soluble in some fluorochemicals. For example, some fluorochemical liquids may dissolve over twenty times a much oxygen and over thirty times as much carbon dioxide as a comparable amount of water. Oxygenatable fluorochemicals act as a solvent for oxygen. They dissolve oxygen at higher tensions and release this oxygen as the partial pressure decreases. Carbon dioxide behaves in a similar manner.
In addition to carrying gases and removing waste products, respiratory promoters such as fluorochemicals may be used as pulmonary drug delivery vehicles, either in conjunction with liquid ventilation or as independent therapy. For example, aerosol delivery systems may rely on a mixture of therapeutically active agents with one or more respiratory promoters to increase dispersion, efficacy and stability of the bioactive agent. Moreover, fluorochemicals have been shown to have pulmonary and systemic antiinflammatory effects. Accordingly, despite relatively high costs, it is desirable to employ fluorochemicals as the respiratory promoter of choice in current liquid ventilation procedures and pulmonary drug delivery.
While liquid ventilation is a significant improvement over conventional ventilation, the escape of fluorochemicals into the environment in the form of vapors gases or aerosols, compromises the effectiveness of PLV therapy. That is, many of the most desirable fluorochemicals are volatile to some extent and naturally evaporate over the course of the treatment. During normal liquid fluorochemical ventilation procedures the generation and release of such vapor may be significant. For example, in current PLV therapy conventional mechanical ventilators release the expired gas, including fluorochemicals, into the environment. In adult PLV treatments evaporative fluorochemical losses may correspond to a significant portion of the material introduced to the lung over the course of the therapy. Of course, if the therapy is to be continued additional respiratory promoter must be added to maintain effective residual volumes. As fluorochemical liquids and other respiratory promoters suitable for liquid ventilation can be relatively expensive, such losses can substantially increase the cost of such treatments. Moreover, the loss of respiratory promoter complicates both dosing regimens and regulation of the current volume of material in the lung.
The problem of fluorochemical loss during liquid ventilation is addressed in co-pending U.S patent application Ser. No. 08/566,023 which is directed to methods and apparatus for closed-circuit ventilation. While the disclosed methods and apparatus are extremely effective at reducing the loss of breathable liquids during liquid ventilation, the equipment necessary to practice the disclosed invention is specialized may not always be available. This is particularly true of situations in less developed countries where the latest medical techniques may not be practiced. Moreover, such equipment can be expensive depending on the configuration of the apparatus and the condition of the patient. Thus, there remains a need by which to retain respiratory promoters and, in particular, breathable liquids during liquid ventilation that is relatively efficient in terms of both cost and ease of use.
Accordingly, it is an object of the present invention to provide simple and cost effective methods of reducing the loss of respiratory promoters, including breathable liquids, during liquid ventilation.
It is another object of the present invention to reduce the loss of respiratory promoters, including breathable liquids, through the use of off-the-shelf components.
It is yet another object of the present invention to provide an apparatus for reducing the loss of a respiratory promoter during liquid ventilation.
It is still another object of the present invention to provide a vapor retention assembly for reducing the loss of pulmonarily introduced fluorochemicals.